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Drug resistance mutations in HIV-2 patients failing raltegravir and influence on dolutegravir response

AuthorsRequena, Silvia; Treviño, Ana; Cabezas, Teresa; García-Delgado, Rosa; Amengual, María José; Lozano, Ana Belén; Peñaranda, María; Fernández, Juan Manuel; Soriano, Vicente; Mendoza, Carmen de
Issue DateJul-2017
PublisherOxford University Press
CitationJournal of Antimicrobial Chemotherapy 72(7): 2083–2088 (2017)
Abstract[Background] A broader extent of amino acid substitutions in the integrase of HIV-2 compared with HIV-1 might enable greater cross-resistance between raltegravir and dolutegravir in HIV-2 infection. Few studies have examined the virological response to dolutegravir in HIV-2 patients that failed raltegravir.
[Methods] All patients recorded in the HIV-2 Spanish cohort were examined. The integrase coding region was sequenced in viraemic patients. Changes associated with resistance to raltegravir and dolutegravir in HIV-1 were recorded.
[Results] From 319 HIV-2-infected patients recorded in the HIV-2 Spanish cohort, 53 integrase sequences from 30 individuals were obtained (20 raltegravir naive and 10 raltegravir experienced). Only one secondary mutation (E138A) was found in one of the 20 raltegravir-naive HIV-2 patients. For raltegravir-experienced individuals, the resistance mutation profile in 9 of 10 viraemic patients was as follows: N155H + A153G/S (four); Y143G + A153S (two); Q148R + G140A/S (two); and Y143C + Q91R (one). Of note, all patients with Y143G and N155H developed a rare non-polymorphic mutation at codon 153. Rescue therapy with dolutegravir was given to 5 of these 10 patients. After >6 months on dolutegravir therapy, three patients with baseline N155H experienced viral rebound. In two of them N155H was replaced by Q148K/R and in another by G118R.
[Conclusions] A wide repertoire of resistance mutations in the integrase gene occur in HIV-2-infected patients failing on raltegravir. Although dolutegravir may allow successful rescue in most HIV-2 raltegravir failures, we report and characterize three cases of dolutegravir resistance in HIV-2 patients, emerging variants Q148K and Q148R and a novel change G118R.
DescriptionSpanish HIV-2 Study Group.
Publisher version (URL)https://doi.org/10.1093/jac/dkx090
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